The long-term objectives of this project are to better understand the contribution of irregular vestibular nerve afferent fibers to the human vestibulo-ocular reflex (VOR), and to understand the functional impact of gentamicin's preferential toxicity on the region of the crista where irregular afferents predominate. During rapid head rotations, while viewing a near target, the VOR gain must increase to account for translation of the eyes with respect to the target. The neural substrate underlying these changes in VOR gain is unclear; however, the observation that this vergence-mediate gain increase is absent for ipsilesional head rotations in patients treated unilaterally with intratympanic gentamicin suggests that irregular vestibular nerve afferents may play a role in active modification of VOR gain (Migliaccio et al., 2004). Unlike regular vestibular afferents, irregular afferents are particularly sensitive to externally applied direct currents and their firing rate can be reduced by galvanic stimulation (Goldberg et al., 1984). Chen-Huang & McCrea (1998) showed in monkeys that when irregular afferents are galvanically inhibited, vergence-mediated modulation of the VOR is also reduced; however, the VOR gain during far viewing is unaffected by galvanic stimulation (Minor and Goldberg, 1991; Karlberg et al., 2000). The first goal of this project is to examine the effects of galvanic inhibition of irregular afferents on the human vergence-mediated VOR gain in normal subjects. If the vergence-mediated VOR gain is reduced during galvanic inhibition, then this would indicate that irregular afferents play an important role in increasing the VOR gain during near viewing. Our second goal is to repeat this experiment in patients treated with intratympanic gentamicin. If during rapid head rotations towards the gentamicin treated ear the vergence-mediated VOR is unaffected by galvanic inhibition, but is increased by galvanic excitation, then this would suggest that modulation of VOR gain by vergence depends upon irregular afferents that are preferentially affected by gentamicin and by galvanic stimuli. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Small Research Grants (R03)
Project #
5R03DC007346-03
Application #
7235374
Study Section
Special Emphasis Panel (ZDC1-SRB-Y (53))
Program Officer
Platt, Christopher
Project Start
2005-07-01
Project End
2008-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
3
Fiscal Year
2007
Total Cost
$77,751
Indirect Cost
Name
Johns Hopkins University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Migliaccio, Americo A; Della Santina, Charles C; Carey, John P (2013) Transmastoid galvanic stimulation does not affect the vergence-mediated gain increase of the human angular vestibulo-ocular reflex. Exp Brain Res 224:489-99
Migliaccio, Americo A; Meierhofer, Robert; Della Santina, Charles C (2011) Characterization of the 3D angular vestibulo-ocular reflex in C57BL6 mice. Exp Brain Res 210:489-501
Migliaccio, Americo A; Minor, Lloyd B; Della Santina, Charles C (2010) Adaptation of the vestibulo-ocular reflex for forward-eyed foveate vision. J Physiol 588:3855-67
Schubert, Michael C; Migliaccio, Americo A; Clendaniel, Richard A et al. (2008) Mechanism of dynamic visual acuity recovery with vestibular rehabilitation. Arch Phys Med Rehabil 89:500-7
Scherer, Matthew; Migliaccio, Americo A; Schubert, Michael C (2008) Effect of vestibular rehabilitation on passive dynamic visual acuity. J Vestib Res 18:147-57
Migliaccio, Americo A; Minor, Lloyd B; Carey, John P (2008) Vergence-mediated modulation of the human angular vestibulo-ocular reflex is unaffected by canal plugging. Exp Brain Res 186:581-7
Migliaccio, Americo A; Schubert, Michael C; Clendaniel, Richard A et al. (2006) Axis of eye rotation changes with head-pitch orientation during head impulses about earth-vertical. J Assoc Res Otolaryngol 7:140-50
Migliaccio, Americo A; Della Santina, Charles C; Carey, John P et al. (2006) The effect of binocular eye position and head rotation plane on the human torsional vestibuloocular reflex. Vision Res 46:2475-86
Schubert, Michael C; Migliaccio, Americo A; Della Santina, Charles C (2006) Modification of compensatory saccades after aVOR gain recovery. J Vestib Res 16:285-91
Schubert, Michael C; Migliaccio, Americo A; Della Santina, Charles C (2006) Dynamic visual acuity during passive head thrusts in canal planes. J Assoc Res Otolaryngol 7:329-38